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P2 receptor-mediated afferent arteriolar vasoconstriction during calcium blockade
Edward W Inscho1, Anthony K Cook
1Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA. einscho@mail.mcg.edu
American Journal of Physiology. Renal Physiology
|January 15, 2002
Summary
L-type calcium channels significantly impact vasoconstriction from ATP but not UTP in afferent arterioles. UTP responses primarily use intracellular calcium stores, while ATP uses both intracellular stores and L-type calcium channels.
Area of Science:
- Nephrology
- Physiology
- Pharmacology
Background:
- Adenosine triphosphate (ATP) and uridine triphosphate (UTP) are purinergic signaling molecules involved in regulating renal hemodynamics.
- P2 receptors, activated by ATP and UTP, play a role in controlling afferent arteriolar tone.
- L-type calcium channels are critical for smooth muscle contraction and vascular tone regulation.
Purpose of the Study:
- To investigate the role of L-type calcium channels in the vasoconstrictor responses of afferent arterioles to ATP and UTP.
- To differentiate the signaling pathways mediating vasoconstriction by alpha,beta-methylene ATP, ATP, and UTP.
- To elucidate the contribution of voltage-dependent calcium influx versus intracellular calcium release in purinergic signaling within the kidney.
Main Methods:
- Utilized the blood-perfused juxtamedullary nephron technique in isolated kidneys.
- Administered alpha,beta-methylene ATP, ATP, and UTP to perfuse arterioles.
- Assessed arteriolar diameter changes before and during blockade of L-type calcium channels with diltiazem.
Main Results:
- alpha,beta-methylene ATP-induced vasoconstriction was abolished by diltiazem, indicating L-type calcium channel dependence.
- UTP-induced vasoconstriction was unaffected by diltiazem, suggesting L-type calcium channels are not involved.
- ATP-induced vasoconstriction was significantly attenuated by diltiazem, particularly at lower concentrations, highlighting a dual mechanism involving L-type calcium channels and intracellular stores.
Conclusions:
- L-type calcium channels are crucial for ATP-mediated afferent arteriolar vasoconstriction but not for UTP-mediated responses.
- UTP primarily triggers vasoconstriction via intracellular calcium release, whereas ATP involves both L-type calcium channel influx and intracellular calcium release.
- P2X and P2Y receptors differentially regulate afferent arteriolar diameter through distinct signal transduction pathways.